Serum proteomic profiling of carotid arteriopathy: A population outcome study

Nicholas Cauwenberghs; Astrid Verheyen; František Sabovčik; Evangelos Ntalianis; Thomas Vanassche; Jana Brguljan; Tatiana Kuznetsova

doi:10.1016/j.atherosclerosis.2023.117331

Serum proteomic profiling of carotid arteriopathy: A population outcome study

Atherosclerosis. 2023 Nov:385:117331. doi: 10.1016/j.atherosclerosis.2023.117331. Epub 2023 Oct 10.

Authors

Nicholas Cauwenberghs¹, Astrid Verheyen², František Sabovčik², Evangelos Ntalianis², Thomas Vanassche³, Jana Brguljan⁴, Tatiana Kuznetsova²

Affiliations

¹ Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven, Belgium. Electronic address: nicholas.cauwenberghs@kuleuven.be.
² Research Unit Hypertension and Cardiovascular Epidemiology, Department of Cardiovascular Sciences, University of Leuven, Belgium.
³ Division of Cardiology, University Hospitals Leuven, Leuven, Belgium.
⁴ Hypertension Department, University Medical Centre Ljubljana, Medical University Ljubljana, Ljubljana, Slovenia.

PMID: 37879154
DOI: 10.1016/j.atherosclerosis.2023.117331

Abstract

Background and aims: Circulating proteins reflecting subclinical vascular disease may improve prediction of atherosclerotic cardiovascular disease (ASCVD). We applied feature selection and unsupervised clustering on proteomic data to identify proteins associated with carotid arteriopathy and construct a protein-based classifier for ASCVD event prediction.

Methods: 491 community-dwelling participants (mean age, 58 ± 11 years; 51 % women) underwent carotid ultrasonography and proteomic profiling (CVD II panel, Olink Proteomics). ASCVD outcome was collected (median follow-up time: 10.2 years). We applied partial least squares (PLS) to identify proteins linked to carotid intima-media thickness (cIMT). Next, we assessed the association between future ASCVD events and protein-based phenogroups derived by unsupervised clustering (Gaussian Mixture modelling) based on proteins selected in PLS.

Results: PLS identified 19 proteins as important, which were all associated with cIMT in multivariable-adjusted linear regression. 8 of the 19 proteins were excluded from the clustering analysis because of high collinearity. Based on the 11 remaining proteins, the clustering algorithm subdivided the cohort into two phenogroups. Compared to the first phenogroup (n = 177), participants in the second phenogroup (n = 314) presented: i) a more unfavorable lipid profile with higher total cholesterol and triglycerides and lower HDL cholesterol (p ≤ 0.014); ii) higher cIMT (p = 0.0020); and iii) a significantly higher risk for future ASCVD events (multivariable-adjusted hazard ratio (95 % CI) versus phenogroup 1: 2.05 (1.26-3.52); p = 0.0093). The protein-based phenogrouping supplemented ACC/AHA 10-year ASCVD risk scoring for prediction of a first ASCVD event.

Conclusions: Focused protein-based phenogrouping identified individuals at high risk for future ASCVD and may complement current risk stratification strategies.

Keywords: Arteriopathy; Carotid intima-media thickness; Carotid ultrasonography; Proteomics; Unsupervised machine learning.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aged
Atherosclerosis* / epidemiology
Cardiovascular Diseases* / epidemiology
Carotid Artery Diseases* / diagnostic imaging
Carotid Artery Diseases* / epidemiology
Carotid Artery Diseases* / genetics
Carotid Intima-Media Thickness
Female
Humans
Male
Middle Aged
Proteomics*
Risk Assessment
Risk Factors